The objective of this investigation will be to determine the central nervous system membrane alterations produced by acute and chronic ethanol and barbiturate administratiaon which occur in a correlative manner to intoxication and the development of tolerance and physical dependence. Specifically, male, Sprague-Dawley rats will be separated into the following treatment groups: control, pairfed control, tolerant, withdrawn and recovered. Whole brains and brain regions (cerebral cortex, cerebellu, brain stem, hypothalamus, midbrain and corpus striatum) will be removed from animals in each treatment group and synaptosomes, synaptosomal plasma membranes (SPM) mitochondria and microsomes will be isolated by ultracentrifugation. Synaptosomes from each treatment group and each brain region will be analyzed for 1) cross-tolerance to barbiturate-and ethanol-induced inhibition of 45Ca++ transport produced by acidic membrane lipids after acute and/or chronic administration of these drugs. In addition, the acute and chronic effects of ethanol and barbiturates will be examined on ATP-dependent 45Ca++ uptake and fatty acid composition of the subcellular organelles listed above. The overall objective will be to determine cellular mechanisms involved in the production of sedation and the deeelopment of tolerance and physical dependence.